The discipline of Clinical Pharmacology seeks to apply an understanding of the fundamental mechanisms of drug action to improve the therapy of human diseases. The Division of Clinical Pharmacology at Vanderbilt offers an outstanding research-based fellowship program committed to training future leaders in the discipline. The mentoring faculty for this postdoctoral training program are 17 faculty members in the Division of Clinical Pharmacology, along with 27 selected faculty members in other departments. Collaborations among investigators focusing on common research themes are well-established in the Division; areas of research focus include 1) Drug metabolism/Pharmacogenetics and pharmacogenomics; 2) Eicosanoid and lipid mediator pharmacology; 3) Vascular biology and control of the circulation; 4) Ion channel pharmacology and arrhythmia pharmacogenomics; 5) Bone and cancer pharmacology; and 6) Pharmacoepidemiology. Additional collaborative efforts exist in pediatrics, cancer pharmacology and neuropharmacology, among others. The primary activity of trainees is research training in a mentored setting on questions directly relevant to drug action in man. Research can vary from bench-based to clinical studies. There are currently 30 postdoctoral fellows in the program and seven are supported by this grant. The duration of training is 2-3 years and individuals holding either an M.D., Ph.D., or Pharm.D. degree are supported. Research training under the direction of individual faculty mentors is supplemented by didactic course work and seminars. Required courses of trainees include research ethics, responsible conduct of research, biostatistics and study design, drug regulation and development, and pharmacokinetics/pharmacodynamics. In addition, attendance at Clinical Pharmacology Grand Rounds and a weekly Fellows' Lecture Series is required. This curriculum supplements the trainees' research experience and provides a broad knowledge base that will allow for fellows to develop into successful leaders in Clinical Pharmacology. Recent commitments by Vanderbilt to grow Clinical Pharmacology offer a unique opportunity to further enhance the training program. These include the opening of the Oates Institute of Experimental Therapeutics and the establishment of the Vanderbilt Center for Bone Biology - both components of the Division of Clinical Pharmacology. The overall mission of the Vanderbilt Clinical Pharmacology training program is to train investigators who will ultimately assume leadership positions in the discipline. Of trainees supported by the award in the past 10 years approximately 90% are in academic medicine, industry or government. Clinical Pharmacology at Vanderbilt is a vibrant and dynamic enterprise poised for significant growth. The excellence of the training program has resulted in substantially more applicants than positions, therefore support for an additional training position per year is requested in this renewal.